DESCRIPTION Mild traumatic brain injury (mTBI) due to exposure to explosive blasts is a common occurrence in veterans returning from recent deployments. Although mTBI is not associated with gross brain damage visible on standard radiological examinations, a subset of individuals report long-term disruptions of cognitive and emotional functioning, suggesting that more subtle neural damage may exist. Given results from civilian mTBI, the damage is likely to be spatially variable across individuals and to affect white matter (WM) tracts connecting distant brain regions. Therefore, measures of brain connectivity may be vital for understanding the neurological effects of deployment-related mTBI (dTBI). In particular, quantification of changes in brain connectivity, rather than simply end-state differences, associated with dTBI may be especially informative. The proposed research plan will investigate deployment-related changes in MRI-based measures of structural and functional connectivity, as well as clinical and neuropsychological measures, in a population of military service members being deployed for the first time. The effect of dTBI on these changes will be tested as well as potential moderating effects of combat stress and other deployment experiences. In addition, the presence of baseline differences in connectivity measures and the effect of these differences on deployment- related changes will be investigated. The overall goals of the proposed research plan are to characterize the neural effects of blast mTBI on brain connectivity and the potential moderating effects of pre-deployment and in-theater factors by pursuing the following aims: Aim 1: To investigate the longitudinal effects of dTBI and deployment experiences on brain connectivity and cognitive performance, as well as the inter-relationships among these changes. Aim 2: To investigate the effects of factors present prior to deployment (e.g. history of civilian mTBI) on pre- deployment brain connectivity and longitudinal changes in connectivity and cognition. The most unique elements of this research plan are the inclusion of neuroimaging data from service members with no prior deployment, the collection of pre- and post-deployment longitudinal neuroimaging data, and the explicit examination of relationships among changes in structural connectivity, functional connectivity, and neuropsychological measures. These elements allow the neural changes associated with deployment in general and bTBI in particular to be characterized in a comprehensive manner. The candidate seeks to use this Career Development experience to build on his existing expertise using neuroimaging methods to study clinical conditions, to develop his skills in clinical assessment of TBI and related conditions, to provide opportunities for VA service, and to establish a rich set of resources for establishing an independent research career within VA. He will accomplish this by working closely with his mentors, administering neuropsychological tests in research and clinical settings, and providing educational, academic, and clinical service to a range of VA centers. The candidate will meet regularly with his mentors throughout the study period to use their wealth of experience to ensure that the study is designed and implemented in a manner most likely to accomplish the proposed aims, contribute to veterans' care, and build a pool of resources that will fuel applications for future funded research. He will engage in a range of training activities that combine coursework with direct patient contact, as well as service activities that include education of clinicians and military leadership, participation in administrative committees (e.g. IRB), and integration of research and clinical aims of the Minneapolis Polytrauma Rehabilitation Center. In addition to providing necessary training and experience in conditions of high relevance to veteran care, these activities will help Dr. Davenport integrate himself with the resources available at the Minneapolis VA Health Care System that will be used to establish an independent VA research career. PUBLIC HEALTH RELEVANCE: The proposed research addresses potential neurological disruptions associated with mild traumatic brain injury (mTBI), or concussion, that results from exposure to an explosive blast. This condition is among the major sources of injury in veterans of recent conflicts and represents a substantial cost in terms of disability and treatment. One of the goals of the proposed research is to establish a biological basis for identifying damage associated with this condition, which would have dramatic implications for diagnosis and differentiation from other conditions such as post-traumatic stress disorder. The other major goal of the proposed research is to characterize the neurological effects of deployment stress and its interaction with blast-related mTBI. The results of these investigations have the potential to contribute valuable information to discussions of how best to protect service members and prevent long-term brain injury.